Abstract 1593: Synergistic effect of SH003 and Docetaxel by targeting a metabolic pathway in non-small cell lung cancer cells

Abstract

Abstract The identification of molecular biomarkers that can predict the response of cancer treatment facilitates more clear targeted therapy by lowering the side effect. Therefore, the present study investigated the key regulatory genes that determine the efficacy of SH003, a herbal medicine, combined with docetaxel (DTX) in non-small cell lung cancer cells. We identified that the combination treatment inhibited the process of the de novo biosynthesis of pyrimidine nucleotide via the reduction of the related enzyme expressions, resulting in DNA damage and apoptosis. However, we found that NSCLC cells have different sensitivities to combination treatment. As a result, the difference in sensitivity was determined by the p53 gene expression pattern of lung cancer cells, indicating that the treatment response of combination enhances by activating p53 in p53 wild-type lung cancer. Lung cancer cells harboring p53 mutations were resistant to the metabolic inhibition by the combination, whereas this effect was restored when p53 is expressed normally. In conclusion, this study revealed the genetic characteristics of cancer cells that are susceptible to treatment response when SH003 and DTX are combined, suggesting that p53 will be an important predictor of combination treatment. Citation Format: Yu-Jeong Choi, Kangwook Lee, Sooyeon Kang, Seo Yeon Lee, Hyun-Ha Hwang, Seong-Gyu Ko. Synergistic effect of SH003 and Docetaxel by targeting a metabolic pathway in non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1593.